In accordance with the objectives outlined for Phase I of the Human Brain Project (PA-93-068), the research proposed in this application focuses on three principal objectives: (1) the development of advanced software modules for quantitative image analysis, (2) the determination of the reliability and validity of the methods and algorithms comprising these modules and, (3) the evaluation of the utility of this software in pilot imaging studies of normal pediatric controls and unique pediatric patient groups with homogeneous genetic or neurobiological causes of neurobiological causes of neurobehavioral dysfunction. The software developed in this project will include modules devoted to multiplanar/volumetric display and rotation, processing and manipulation of data within a three-dimensional (3D) environment, segmentation, filtering, interpolation, and data importation. Software modules will include source code components from the public domain program,NIH Image, as well as additional/enhanced code permitting 3D image manipulation, processing and analysis. The reliability and validity of the techniques and methods developed for this aim will be tested with scans of simple and complex phantoms as well as scans and corresponding neuroanatomic sections obtained from humans and primate brains. Modules will be made available in the public domain and will be written in C++ to be cross- platform compatibility as well. The rewritten shell will permit more advanced capabilities such as parallel and distribute processing, 16 bit data handling and direct linkage and communication with database programs. Collaborative relationships for software feasibility testing and co-development have been initiated with several other imaging laboratories both within and outside the Johns Hopkins-Kennedy Kreiger Institutes to facilitate the software development described in this application. To provide initial information about the effectiveness of the software when applied to pilot clinical studies, the methods and techniques developed will be used to construct preliminary quantitative atlases of cortical and subcortical brain maturation in childhood. The software will also be used to differentiate neuroanatomical profiles of pediatric patient groups with homogeneous genetic and/or neurobiological causes of brain dysfunction from age-and gender-matched normal subjects. Because of he availability of scans and corresponding neurobehavioral and genetic data from these unique pediatric patient groups, the testing of more specific hypotheses regarding brain-behavior associations will be possible.